Neonatal brain injury remains a major cause of morbidity and mortality for premature infants, with up to 50% of infants having cognitive and/or behavioral problems by school age. While many studies have focused on white matter abnormalities as the cause of this dysfunction, there is mounting evidence that premature infants also sustain significant injury to cerebral cortical grey matter. We propose to develop and apply MR diffusion methods to evaluate cortical organization. The methods to be used are based on high-angular resolution diffusion imaging (HARD) and q-space diffusion imaging (QSI). Both methods permit detailed, three-dimensional assessments of water displacement. QSI requires more extensive data acquisition than HARD. As a result, HARD data acquisition schemes are more amenable to use in human subjects. HARD data will be analyzed via spherical harmonic decomposition. QSI data will be analyzed via generation of probability density functions by three-dimensional Fourier transformation. The proposed studies are divided into two general categories. The first involves evaluation of fixed human autopsy tissue. Both QSI and HARD data will be obtained to determine the relationship between HARD and QSI anisotropy measures as well as suggest optimum data acquisition parameters for study of live infants. They will also be used to delineate the progression of diffusion anisotropy parameters during cortical maturation. The second category is the acquisition of HARD data from live infants. This will entail optimization of HARD data acquisition parameters. In addition, anisotropy values from occipital cortex will be compared between normal, term control infants and preterm infants at term-equivalent. This will provide information regarding the effects of prematurity on cortical development. Anisotropy values will also be compared between premature infants at term-equivalent with and without white matter injury to evaluate associations between white matter injury and cortical disruption. If successful, these methods will provide a potential means of identifying the nature and extent of cortical injury in premature infants. They may also allow identification of infants at risk for subsequent neurodevelopmental disability at the time the infants are discharged from the hospital.